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Gene Review

SLC13A2  -  solute carrier family 13 (sodium-dependent...

Homo sapiens

Synonyms: NADC1, Na(+)/dicarboxylate cotransporter 1, NaCT, NaDC-1, Renal sodium/dicarboxylate cotransporter, ...
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Disease relevance of SLC13A2

  • Restriction endonuclease maps were constructed for the genome of a porcine adenovirus (PAV), NADC-1, which was isolated in 1972 from an adult swine [1].
  • Using the cloned NADC-1 Bam HI and Eco RI/Bam HI fragments as probes, Southern blot hybridizations were performed to human adenovirus 2 (Ad-2) restriction fragments to determine the left-to-right orientation of the Bam HI and Eco RI/Bam HI fragments [1].
  • Several phage-resistant isolates carried a phage that lysed the stock strain of C. fetus subsp. jejuni (NADC 917) [2].
  • SDCT (100 mAs effective tube current) and LDCT (20 mAs) of nine patients with pulmonary metastases were obtained within 5 min using four-row detector CT [3].
  • The dose-length product (DLP) was estimated for 15 randomly chosen single-detector CT (SDCT) and MDCT adult flank pain examinations using manufacturer's software [4].

High impact information on SLC13A2

  • SDCT2, unlike SDCT1, displayed a unique pH dependence for succinate transport (optimal pH 7.5-8.5) and showed a high affinity for dimethylsuccinate, two features characteristic of basolateral transport [5].
  • The low affinity Na+/sulfate cotransporter, NaSi-1, belongs to the SLC13 family that also includes the Na+/dicarboxylate cotransporters, NaDC [6].
  • The Na+/dicarboxylate cotransporter 1 (NaDC1) is a low-affinity transporter for citric acid cycle intermediates such as succinate and citrate [7].
  • The sequence of NaDC1 contains a number of conserved proline residues in predicted transmembrane helices (TMs) 7 and 10 [7].
  • Four conserved proline residues in TMs 7 and 10 of rabbit NaDC1 were replaced with alanine to promote ideal alpha helix or glycine to promote free conformation, and the mutant transporters were expressed in the HRPE cell line [7].

Biological context of SLC13A2


Anatomical context of SLC13A2

  • Proximal tubule cells extract dicarboxylates from filtrate and blood, using cotransporters located in the brush border [sodium dicarboxylate cotransporter (NaDC-1)] and basolateral cell membrane (NaDC-3) [9].
  • Xenopus oocytes injected with hNaDC-1 cRNA expressed a low-affinity Na(+)-dependent dicarboxylate transporter with Michaelis constant (Km) for succinate around 0.4 mM [10].
  • The above-mentioned studies suggest that human SDCT1 protein is located on the lumen membrane of the renal proximal tubule, the C-terminal sequence of the SDCT1 is required for delivery and targeting localization, and the plasma membrane localization signal of the SDCT1 protein maybe locate in the C-terminal sequence [11].
  • Recently, the complementary DNAs coding for the Na+/citrate transporters from the apical membranes of rabbit and human kidney, NaDC-1 and hNaDC-1, have been cloned and sequenced [12].
  • Expression of the renal Na+/dicarboxylate cotransporter, NaDC-1, in COS-7 cells [13].

Associations of SLC13A2 with chemical compounds

  • The transport of succinate by hNaDC-1 was insensitive to the pH of the medium, whereas the transporter of citrate was stimulated by acidic pH [10].
  • Two serine residues in hNaSi-1, at positions 260 and 288, are conserved in all of the sulfate transporters in the family whereas the NaDC contain alanine or threonine at those positions [6].
  • Then, EGFP-fused wild-type, NH2- and COOH-terminal deletion and point mutants of NaDC3, and chimera between NaDC3 and NaDC1, were generated and transfected into polarized renal cells lines, LLC-PK1 and MDCK [14].
  • The other members of the family (NaDC1, NaDC3, and NaCT) are transporters for di- and tri-carboxylates including succinate, citrate and alpha-ketoglutarate [15].
  • The unfolding of human apolipoprotein B-100 in its native lipid environment, low density lipoprotein (LDL), and in a soluble, lipid-free complex with sodium deoxycholate (NaDC) has been examined using differential scanning calorimetry (DSC) and near UV circular dichroic (CD) spectroscopy [16].

Other interactions of SLC13A2

  • The human Na+-sulfate cotransporter (hNaSi-1) belongs to the SLC13 gene family, which also includes the high-affinity Na+-sulfate cotransporter (hSUT-1) and the Na+-dicarboxylate cotransporters (NaDC) [17].
  • Western blot analysis of biotinylated oocyte surface membranes revealed that the co-expression of ClC-5 with ENaC, CFTR, or NaDC-1 decreased the abundance of these proteins at the surface membrane [18].

Analytical, diagnostic and therapeutic context of SLC13A2

  • EGFP/SDCT1 mRNAs obtained by in vitro transcription are microinjected into Xenopus laevis oocytes for expression and the trans-membrane currents are measured by using two-microelectrode voltage-clamp technique [11].
  • Northern blot analysis indicates that hNaDC-1 mRNA is found in both kidney and intestine [10].
  • Using cloned NADC-1 genomic fragments as probes in Southern blot hybridizations, an RE site map was constructed [1].
  • Differential scanning calorimetry (DSC) and circular dichroic spectroscopy (CD) were used to investigate the physical properties of apoB in the mixed micellar complex with NaDC and in the vesicular DMPC-apoB complex [19].
  • Negative staining experiments were performed in two ways: 1) grids were pulled through NaDC-containing buffer surfaces on which monolayers of apoB had been promoted, or 2) apoB molecules were allowed to diffuse onto carbon surfaces of grids that were floated on sample droplets [20].


  1. Genomic cloning and restriction site mapping of a porcine adenovirus isolate: demonstration of genomic stability in porcine adenovirus. Kleiboeker, S.B., Seal, B.S., Mengeling, W.L. Arch. Virol. (1993) [Pubmed]
  2. Detection of enteric campylobacteriosis in children. Bokkenheuser, V.D., Richardson, N.J., Bryner, J.H., Roux, D.J., Schutte, A.B., Koornhof, H.J., Freiman, I., Hartman, E. J. Clin. Microbiol. (1979) [Pubmed]
  3. Detection of pulmonary nodules at multirow-detector CT: effectiveness of double reading to improve sensitivity at standard-dose and low-dose chest CT. Wormanns, D., Ludwig, K., Beyer, F., Heindel, W., Diederich, S. European radiology. (2005) [Pubmed]
  4. Radiation dose associated with unenhanced CT for suspected renal colic: impact of repetitive studies. Katz, S.I., Saluja, S., Brink, J.A., Forman, H.P. AJR. American journal of roentgenology. (2006) [Pubmed]
  5. Molecular and functional analysis of SDCT2, a novel rat sodium-dependent dicarboxylate transporter. Chen, X., Tsukaguchi, H., Chen, X.Z., Berger, U.V., Hediger, M.A. J. Clin. Invest. (1999) [Pubmed]
  6. Serines 260 and 288 are involved in sulfate transport by hNaSi-1. Li, H., Pajor, A.M. J. Biol. Chem. (2003) [Pubmed]
  7. Role of conserved prolines in the structure and function of the Na+/dicarboxylate cotransporter 1, NaDC1. Joshi, A.D., Pajor, A.M. Biochemistry (2006) [Pubmed]
  8. Assignment of the sodium-dependent dicarboxylate transporter gene (SLC13A2 alias NaDC-1) to human chromosome region 17p11.1-->q11.1 by radiation hybrid mapping and fluorescence in situ hybridization. Mann, S.S., Hart, T.C., Pettenati, M.J., von Kap-herr, C., Holmes, R.P. Cytogenet. Cell Genet. (1999) [Pubmed]
  9. Substrate specificity of the human renal sodium dicarboxylate cotransporter, hNaDC-3, under voltage-clamp conditions. Burckhardt, B.C., Lorenz, J., Kobbe, C., Burckhardt, G. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  10. Molecular cloning and functional expression of a sodium-dicarboxylate cotransporter from human kidney. Pajor, A.M. Am. J. Physiol. (1996) [Pubmed]
  11. Expression of EGFP/SDCT1 fusion protein, subcellular localization signal analysis, tissue distribution and electrophysiological function study. Bai, X., Chen, X., Fen, Z., Wu, D., Hou, K., Cheng, G., Peng, L. Sci. China, C, Life Sci. (2004) [Pubmed]
  12. Citrate transport by the kidney and intestine. Pajor, A.M. Semin. Nephrol. (1999) [Pubmed]
  13. Expression of the renal Na+/dicarboxylate cotransporter, NaDC-1, in COS-7 cells. Pajor, A.M., Valmonte, H.G. Pflugers Arch. (1996) [Pubmed]
  14. Identification of basolateral membrane targeting signal of human sodium-dependent dicarboxylate transporter 3. Bai, X., Chen, X., Feng, Z., Hou, K., Zhang, P., Fu, B., Shi, S. J. Cell. Physiol. (2006) [Pubmed]
  15. Molecular properties of the SLC13 family of dicarboxylate and sulfate transporters. Pajor, A.M. Pflugers Arch. (2006) [Pubmed]
  16. Calorimetric and spectroscopic investigation of the unfolding of human apolipoprotein B. Walsh, M.T., Atkinson, D. J. Lipid Res. (1990) [Pubmed]
  17. Mutagenesis of the N-glycosylation site of hNaSi-1 reduces transport activity. Li, H., Pajor, A.M. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  18. ClC-5 chloride channel alters expression of the epithelial sodium channel (ENaC). Mo, L., Wills, N.K. J. Membr. Biol. (2004) [Pubmed]
  19. Physical properties of apoprotein B in mixed micelles with sodium deoxycholate and in a vesicle with dimyristoyl phosphatidylcholine. Walsh, M.T., Atkinson, D. J. Lipid Res. (1986) [Pubmed]
  20. Morphology of sodium deoxycholate-solubilized apolipoprotein B-100 using negative stain and vitreous ice electron microscopy. Gantz, D.L., Walsh, M.T., Small, D.M. J. Lipid Res. (2000) [Pubmed]
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